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==Crystal structure of wild-type HIV-1 protease with novel tricyclic P2-ligands GRL-0739A== | ==Crystal structure of wild-type HIV-1 protease with novel tricyclic P2-ligands GRL-0739A== | ||
<StructureSection load='4kb9' size='340' side='right' caption='[[4kb9]], [[Resolution|resolution]] 1.29Å' scene=''> | <StructureSection load='4kb9' size='340' side='right'caption='[[4kb9]], [[Resolution|resolution]] 1.29Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4kb9]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4kb9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KB9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KB9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G79:(3AR,3BR,4S,7AR,8AS)-DECAHYDROFURO[2,3-B][1]BENZOFURAN-4-YL+[(2S,3R)-3-HYDROXY-4-{[(4-METHOXYPHENYL)SULFONYL](2-METHYLPROPYL)AMINO}-1-PHENYLBUTAN-2-YL]CARBAMATE'>G79</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.29Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G79:(3AR,3BR,4S,7AR,8AS)-DECAHYDROFURO[2,3-B][1]BENZOFURAN-4-YL+[(2S,3R)-3-HYDROXY-4-{[(4-METHOXYPHENYL)SULFONYL](2-METHYLPROPYL)AMINO}-1-PHENYLBUTAN-2-YL]CARBAMATE'>G79</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4kb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kb9 OCA], [https://pdbe.org/4kb9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kb9 RCSB], [https://www.ebi.ac.uk/pdbsum/4kb9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kb9 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q7SSI0_9HIV1 Q7SSI0_9HIV1] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 17: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4kb9" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Agniswamy J]] | ||
[[Category: | [[Category: Wang Y-F]] | ||
[[Category: Weber IT]] | |||
[[Category: | |||
Latest revision as of 18:57, 20 September 2023
Crystal structure of wild-type HIV-1 protease with novel tricyclic P2-ligands GRL-0739ACrystal structure of wild-type HIV-1 protease with novel tricyclic P2-ligands GRL-0739A
Structural highlights
FunctionPublication Abstract from PubMedThe design, synthesis, and biological evaluation of a series of HIV-1 protease inhibitors incorporating stereochemically defined fused tricyclic P2 ligands are described. Various substituent effects were investigated to maximize the ligand-binding site interactions in the protease active site. Inhibitors 16a and 16f showed excellent enzyme inhibitory and antiviral activity, although the incorporation of sulfone functionality resulted in a decrease in potency. Both inhibitors 16a and 16f maintained activity against a panel of multidrug resistant HIV-1 variants. A high-resolution X-ray crystal structure of 16a-bound HIV-1 protease revealed important molecular insights into the ligand-binding site interactions, which may account for the inhibitor's potent antiviral activity and excellent resistance profiles. Highly Potent HIV-1 Protease Inhibitors with Novel Tricyclic P2 Ligands: Design, Synthesis, and Protein-Ligand X-ray Studies.,Ghosh AK, Parham GL, Martyr CD, Nyalapatla PR, Osswald HL, Agniswamy J, Wang YF, Amano M, Weber IT, Mitsuya H J Med Chem. 2013 Aug 15. PMID:23947685[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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